The multifactorial etiology of otitis media with effusion (OME), the many sources for the variety of inflammatory substances contained in the effusions and the poor understanding of the contribution of these substances to the inflammatory and immune processes frustrates attempts to design targeted interventions. For these reasons, OME is often refractory to treatment. Studies of clinical material cannot be used to address this as the underlying etiology is not known. However, a number of animal models have been developed to represent each of the posited etiologic factors. The experiments outlined in this proposal utilize these animal models to define specific biochemical profiles and their evolution with time for each etiology. Assays for inflammatory mediators, free fatty acids, proteolytic enzymes, hydrolytic enzymes and immune response will be included as variables and the profiles will be determined by linear discriminant function analysis. Then for each model the effect of specific interventional probes which alter select aspects of the biochemical cascade associated with the arachidonic acid metabolic pathway and inflammation will be defined. These interventions will be evaluated by documenting: 1) the changes in the respective biochemical profiles; 2) the effects on select aspects of the immune system, and 3) the possible changes in disease course determined by otomicroscopy, tympanometry and histopathology. These experiments will serve to: 1) identify the role of the inhibited or modulated targets of the probes in initiating and/or sustaining the inflammatory processes culminating in OME, and 2) define etiology specific therapeutic strategies for later evaluation in the clinical setting. Finally, as an inhibitor of mitogen stimulated lymphocyte proliferation is present in middle ear effusion (MEE) from patients with OME, experiments are planned to demonstrate the presence of such an inhibitor in experimental MEE and to biochemically characterize this substance.